Neurodegenerative diseases are one kind of chronic, progressive neurological diseases, generally characterized by delayed neuronal degenerative lesion and cell loss in specific regions. It is caused by the loss of neurons or their myelin sheath, and will worsen over time, resulting in dysfunction. The neurodegenerative diseases are generally divided into two categories according to their phenotype, one is affecting movement, such as cerebellar ataxia, Parkinson's disease, and the other is Dementia that affects memory and its related function. At present, the therapeutic drug for neurodegenerative diseases is still fewer.
Senile dementia is one of the neurodegenerative diseases, and is heterogeneous disease with multiple etiologies. It is a central nervous system degenerative disease syndrome characterized by progressive cognitive dysfunction and memory impairment, behaving as a decrease in intelligence (including memory, learning ability, direction recognition ability, language ability, comprehension and judgment ability). This disease is affected by many factors (including biological and psychosocial factors). There are as many as 30 possible pathogenetic factors and hypotheses, such as family history, head trauma, thyroid disease, and viral infection. Senile dementia is commonly seen as Alzheimer's disease (AD), Vascular dementia (VA), Dementia with Lewy bodies (DLB), and Frontotemporal dementia (FTD). In all patients with dementia, Alzheimer's disease accounted for 50 to 70%, which is the most common type of Senile dementia.
The treatment of Senile dementia is mainly divided into: (1) the symptomatic treatment by controlling the concomitant psychopathological states with the medication mainly including anxiolytic drugs such as alprazolam, oxazepam, triazolam; antidepressants, such as Prozac, paroxetine, sertraline; antipsychotics such as risperidone, olanzapine, (2) the improvement of intelligence or cognitive function with the medication mainly including acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists (NMDA), estrogens, and drugs for promoting brain metabolism. These drugs can improve the patient's dementia symptoms to a certain extent, but they cannot fundamentally prevent the deterioration of the disease and reverse the disease. Therefore, the search for anti-Senile dementia drugs has attracted worldwide attention, and many related biological activity screening and evaluation systems have been established. Among numerous existing whole animal models, fruit fly is one of the most well-known model organisms. The fruit fly has advantages that cannot be matched by other animal models, for example, extremely small individual space occupancy (in general, thousands fruit flies can be cultured in a single reagent bottle), low feeding costs, easy culture, rapid reproduction and strong reproductive capacity (high screening throughput), low sample consumption (5-50 mg), short life cycle (about 50 days, short activity test cycle), evident age-related neuronal deterioration. Thus it is desired model for the study and drug screening for neurodegenerative diseases such as Senile dementia.
Dicaffeoyl spermidine derivatives are a rare class of plant components that are currently under-researched. There have been no previous reports on dicaffeoyl spermidine cyclized derivatives. The present invention is the discovery and isolation of a class of dicaffeoyl spermidine cyclized derivatives from fructus lycii, and has been demonstrated by the fruit fly model that it has the activity of preventing and treating neurodegenerative diseases, especially senile dementia.